1. Field of the Invention
The present invention is related to the field of microelectronic devices, designed to transport and manipulate magnetic beads on chip. Application domains are biochips, biosensors, diagnostics, genetics and molecular studies.
2. Description of the Related Art
Following the publication of the first draft of the human genome sequence, the next major task is to determine the function that each of the genes (i.e. >35,000) have in each of the tissues in the body over a range of environmental conditions. Using arrays of thousands of probes which are specific to individual genes, DNA microarrays enable the extent to which individual genes are switched on or off to be determined. Genetic variation among individuals also contributes to variation in the way genes behave in response to changes in the environment. Simultaneous detection of variation at thousands of locations (i.e. single nucleotide polymorphisms or SNPs) in the genome can also be achieved using DNA microarray technology. Applications of DNA microarrays therefore include gene expression profiling, gene sequencing, gene discovery, and genotyping, for users in healthcare, academia and the pharmaceutical and biotechnology industries. Currently the major factors limiting the uptake of DNA microarray technology include low sensitivity, the high cost of the technology, requirement for specialist operators and throughput.
Electronic biochips have the potential to overcome these limitations. Here, exploitation of state-of-the-art micro- and nano-technology design, fabrication and characterization tools and processes enable development of devices and systems that can interface directly with biological reactions. A possibility involves combining magnetic bead-based bioassays with magnetic sensor technology. From a biotechnology perspective, paramagnetic beads (e.g., 0.05–10.0 μm diameter) are available commercially from a number of sources with a range of surface functional chemistries, for well established applications including isolation and transportation of nucleic acids, proteins and whole cells. In microelectronics, GMR-based magnetic sensors have provided an enabling technology for memory applications. Thus, integration of paramagnetic bead-based nucleic acid assays on a functional biochip surface incorporating magnetic sensors, provides the basis for a range of biochip platforms.
Next to the detection of the magnetic beads, the transport and manipulation of beads is a limiting factor, which has to be taken into account in biochip designs and methods.
In the past, systems have been described for the manipulation of magnetic microbeads based on permanent or electromagnets with dimensions >5 mm, which did not allow for magnetic fields localised over microscale regions.
Commercial devices exist for sorting and separation of magnetic microbeads, but they have a limited capability of performing complex manipulations of these beads since they make use of permanent magnets or electromagnets.
In Whitesides et al., “Manipulation of magnetic microbeads in suspension using micromagnetic systems fabricated with soft lithography”, Applied Physics Letters [Vol 78, Nr 12 Mar. 19, 2001, pages 1775–1777] and US2002/0166800, systems are described comprising current carrying wires that can generate strong local magnetic field gradients, which in their turn can control the position of magnetic microbeads in aqueous suspension.